Project Summary Candidate: Dr. Slogrove is unwaveringly committed to a career focused on finding solutions to maternal and child health challenges in low-middle income countries (LMIC). She ultimately envisions herself globally as a leader in HIV exposed uninfected (HEU) child research and locally as the leader of a rural maternal and child health research unit. Dr. Slogrove?s 5-year career development plan is focused on three specific areas: 1) to develop advanced epidemiologic skills building on doctoral and post-doctoral studies in epidemiology; 2) to strengthen leadership ability; 3) to expand maternal health expertise complementing pediatric specialist training to comprehensively research the maternal-child dynamic. This will be achieved through drawing on the strengths of four leading institutions with strong collaborative ties, Stellenbosch University, University of Cape Town, Columbia University and Harvard. Dr. Slogrove has assembled a highly experienced mentorship team combining expertise in maternal and child HIV clinical research with public health, epidemiology and biostatistics. Research: This study aims to understand epidemiologically whether HIV and antiretroviral therapy (ART) are associated with hypertensive disorders in pregnancy (HDP) and whether this represents a pathway to adverse maternal, birth and HEU infant outcomes. The specific aims are to determine: 1) whether maternal HIV and antenatal ART are associated with HDP; 2) the contribution of HDP in HIV-infected women to adverse maternal and birth outcomes; 3) the contribution of maternal morbidity and mortality and adverse birth outcomes to HEU neonatal and infant morbidity and mortality. This early career award study will be integrated within the NICHD-funded B-POSITIVE study, comprehensively evaluating the universal maternal ART strategy at a population level in the entire Western Cape Province of South Africa. Provincial surveillance through harmonization of existing provincial electronic routine data sources is combined with sentinel-site activities to investigate population trends in greater depth. This presents a unique opportunity to interrogate pathways of HEU infant vulnerability in a population where 19% of infants are in utero HIV and ART exposed. The current application utilizes the B-POSITIVE electronic harmonized data platform to evaluate the specific aims at a population level in the entire cohort of pregnant women in the Western Cape for a 2-year period (N?190,000) and in greater depth at two sentinel sites (N?17,000). Mediation analysis will be used to understand whether the adverse birth outcomes associated with antenatal ART are partly mediated by increased HDP and in turn whether they partly mediate neonatal and infant morbidity and mortality. This study will rapidly determine in an entire population whether widely used antenatal ART regimens are associated with HDP and whether this represents a pathway to adverse maternal and birth outcomes leading to excess HEU infant morbidity and mortality. Establishing the safety of ART during pregnancy is of critical public health importance for the 30% of pregnant South African women who are HIV-infected.